Nearly half of the estimated 5 million (projected to be 10 million by 2040) heart failure (HF) patients in the United States have diastolic HF or HF with normal or near-normal left ventricular ejection fraction. Most of these patients are older adults, for whom HF is the leading (~1 million per year) cause for hospitalization. The overall prognosis of diastolic HF is very similar to systolic HF or HF with moderately to severely reduced left ventricular ejection fraction. Yet, diastolic HF patients have traditionally been excluded from major randomized clinical trials (RCTs) of HF and there is little evidence to guide therapy for these patients. Our immediate goal is to study the long-term effects of three neurohormonal antagonists: angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), beta-blockers and aldosterone antagonists, in three propensity-matched populations of Organized Program to Initiate Life-Saving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) participants with diastolic HF. The OPTIMIZE-HF is a large (N=48,612, n for diastolic HF=21,149), contemporary (2003-2004) and national (involving 259 hospital from 48 states) database of real-life hospitalized HF patients who have often been excluded from large RCTs. We will work with the Research Data Assistance Center (ResDAC) to obtain long-term data on mortality and hospitalization from the Center for Medicare and Medicaid Services (CMS) and study the associations of neurohormonal blockade and long-term outcome in eligible patients. We hypothesize that neurohormonal blockade with angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), beta-blockers or aldosterone antagonists will reduce mortality and hospitalization in these patients. We base our hypothesis on the observations that despite differences in nature of left ventricular dysfunction, the pathogenesis (including neurohormonal activation), clinical presentation, and outcomes in systolic and diastolic HF are very similar and therapy with these three neurohormonal modulators have been shown to reduce mortality and hospitalization in systolic HF. It would be ideal to have definitive RCTs to study the effect of neurohormonal blockade in diastolic HF. However, when RCTs are either unethical or impractical, well-designed observational studies can provide data to derive best practice methods. Propensity score matching has recently emerged as a tool to design non-RCT studies like RCTs in which investigators are blinded to study outcomes during study design. Our long-term goal is to provide evidence that will guide clinical guidelines and practice for the management of diastolic HF, who comprise half of all HF patients, and improve quality and outcomes of care for these patients. PUBLIC HEALTH RELEVANCE: Nearly half of all heart failure patients have diastolic heart failure, which have similar prognosis as in systolic heart failure. Neurohormonal antagonists improve outcomes in systolic heart failure but there is no evidence regarding their effect in diastolic heart failure. The proposed study will examine the effect of neurohormonal blockade in propensity matched OPTIMIZE-HF participants with diastolic heart failure.